Food allergy affects about 6-8% of children younger than four years of age, and about 2% of the United States population over ten years old, and the prevalence appears to be increasing. See Sampson H A. Food allergy. Part 1: Immunopathogenesis and Clinical Disorders. J. Allergy Clin. Immunol. 1999; 103:717-728. Food allergy is now the leading cause of anaphylactic reactions (approximately 31,000 cases annually) treated in hospital emergency departments in the United States. See Sampson H A. Clinical practice. Peanut allergy. N Engl J Med 2002; 346:1294-1299. It is known that only 8 foods account for 90 percent of the allergic reactions. They include peanuts, tree nuts (walnuts, pecans, etc.), fish, shellfish, eggs, milk, soy, and wheat. However, peanuts are the leading cause of severe allergic reactions, followed by shellfish, fish, tree nuts, and eggs.
Allergic reactions occur when an individual's immune system overreacts, or reacts inappropriately, to an encountered antigen. No allergic reaction is thought to occur the first time an individual is exposed to a particular antigen. However, the initial immune response to an antigen primes the system for subsequent allergic reactions. In particular, the antigen is taken up by antigen presenting cells (e.g., macrophages or dendritic cells) that degrade the antigen and then display antigen fragments to T cells. The activated T cells respond by secreting a collection of cytokines that affect other cells of the immune system. The profile of cytokines secreted by responding T cells determines whether subsequent exposures to the particular antigen will induce allergic reactions. When T cells respond by secreting interleukin-4 (IL-4), the effect is to stimulate the maturation of B cells that produce IgE antibodies specific for the antigen. These antigen-specific IgE antibodies then attach to specific receptors on the surface of mast cells and basophils, where they act as a trigger to initiate a rapid reaction to subsequent exposures to the antigen.
When the individual next encounters the antigen, it is quickly bound by these surface associated IgE molecules. Each antigen typically has more than one IgE binding site, so that the surface bound IgE molecules quickly become cross-linked to one another through their simultaneous (direct or indirect) associations with antigen. Such cross-linking induces mast cell degranulation, resulting in the release of histamines and other substances that induce the symptoms associated with allergic reaction. Individuals with high levels of IgE antibodies are known to be particularly prone to allergies.
Peanut allergy, which account for two thirds of cases of fatal anaphylactic shock, develops at an early age where the first reactions occur at a median age of 14 months. See Bock S A, Munoz-Furlong A, Sampson H A. Fatalities due to anaphylactic reactions to foods. J. Allergy Clin. Immunol. 2001; 107:191-193; and Sicherer S H, Furlong T J, Munoz-Furlong A, Burks A W, Sampson H A. A voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants. J Allergy Clin Immunol 2001; 108:128-132. Most anaphylactic reactions to peanuts (PN) occur in preschool and day care, and school exposure represents the first reaction for 25% of these children. See Sicherer S H, Furlong T J, DeSimone J, Sampson H A. The US Peanut and Tree Nut Allergy Registry: characteristics of reactions in schools and day care. J Pediatr 2001; 138:560-565. Because of these features of peanut allergy and because most PN allergic reactions are caused by inadvertent ingestion, peanut allergy has a severe negative effect on the quality of life of children and their families. See Primeau M N, Kagan R, Joseph L, Lim H, Dufresne C, Duffy C, Prhcal D, Clarke A. The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut-allergic children. Clin Exp Allergy 2000; 30:1135-1143.
Peanut allergy is an IgE mediated type I hypersensitivity in which allergen-specific IgE antibodies that bind to high affinity receptors (FcεRI) on the surface of mast cells and basophils. In patients with food allergy, re-exposure to the relevant foods triggers degranulation of mast cells/basophils resulting in the release of histamine and other mediators, which provoke symptoms of anaphylaxis. Early symptoms of food-induced anaphylaxis often include oral pruritus, colicky abdominal pain, nausea, vomiting, and diarrhea, cutaneous flushing, urticaria, and angioedema. Progressive respiratory symptoms, hypotension, and dysrhythmias typically develop in fatal and near fatal cases. See Yocum M W, Butterfield J H, Klein J S, Volcheck G W, Schroeder D R, Silverstein M D. Epidemiology of anaphylaxis in Olmsted County: A population-based study. J. Allergy Clin. Immunol. 1999; 104:452-456. Numerous studies have shown that Th2 cytokines are central to the pathogenesis of allergic disorders. See Romagnani S. The role of lymphocytes in allergic disease. J. Allergy Clin. Immunol. 2000; 105:399-408.
At the present time, there is no treatment for PN allergy. In the case of severe anaphylactic shock, epinephrine is often administered, either by self-injection (e.g. using the Epi-Pen®) or as an emergency treatment. Epinephrine rapidly constricts the blood vessels, relaxes the muscles in the airway and lungs, reverses swelling, and stimulates heartbeat, thereby reversing the most dangerous effects of an anaphylactic reaction. However, this treatment does not treat the allergic disorder itself. Furthermore, side effects of epinephrine may be severe and include palpitations, tachycardia (an abnormally fast heartbeat), sweating, nausea and vomiting, and respiratory difficulty and cardiac arrhythmias may follow administration of epinephrine.
Traditional immunotherapy is not an option for peanut allergy because of the high incidence of adverse reactions and low rate of maintenance of tolerance. See Nelson P A, Akselband Y, Dearborn S M, al-Sabbagh A, Tian Z J, Gonnella P A, Zamvil S S, Chen Y, Weiner H L. Effect of oral beta interferon on subsequent immune responsiveness. Ann. N.Y. Acad. Sci. 1996; 778:145-155; and Nelson H S, Lahr J, Rule R, Bock A, Leung D. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J. Allergy Clin. Immunol. 1997; 99:744-751. The only way to manage peanut allergy is strict avoidance, but PN is a hidden ingredient in a number of processed foods and accidental ingestions are common. See Tariq S M, Stevens M, Matthews S, Ridout S, Twiselton R, Hide D W. Cohort study of peanut and tree nut sensitisation by age of 4 years. BMJ 1996; 313:514-517; and Bock S A. The natural history of food sensitivity. J Allergy Clin Immunol 1982; 69:173-177. Furthermore, up to 55% of PN allergic children over a period of 5.4 years experience reactions following accidental ingestion. See Sicherer S H, Burks A W, Sampson H A. Clinical features of acute allergic reactions to peanut and tree nuts in children. Pediatrics 1998; 102:e6. This makes it urgent to develop approaches for peanut allergy.
Several new approaches to food allergy treatment are under. See Sampson H A. Immunological approaches to the treatment of food allergy. Pediatr Allergy Immunol 2001; 12:91-96; and Li X. M., Sampson H A. Novel approaches for the treatment of food allergy. Current Opinion in Allergy and Clinical Immunology 2002; 2:273-278. An ongoing clinical trial using monthly injections of humanized recombinant anti-IgE, appears to be somewhat effective in preventing allergic responses in PN-sensitive subjects to small amounts of PN protein. However, this treatment cannot cure the allergy, and continued protection would depend on monthly injections for an indefinite period of time.
One approach to treating allergies is antigen immunotherapy, which attempts to “vaccinate” a sensitive individual against a particular allergen by periodically injecting or treating the individual with a crude suspension of the raw allergen. The goal is to modulate the allergic response mounted in the individual through controlled administration of known amounts of antigen. If the therapy is successful, the individual's allergic response is diminished, or can even disappear. However, the therapy can require several rounds of vaccination, over an extended time period (3 to 5 years), and very often does not produce the desired results. Moreover, certain individuals suffer anaphylactic reactions to the vaccines, despite their intentional, controlled administration.
Another commonly used approach to treating allergic symptoms is the administration of histamine antagonists. These drugs are widely available in over-the-counter formulations, but unfortunately they merely mask the symptoms of the allergic response rather than providing any type of permanent cure or protection against recurrence.
Traditional Chinese Medicine (TCM) is one of the oldest medical practices in the world. The theoretical foundation of TCM described in Yellow Emperor's Inner Classic is believed to have been established in the first or second century C.E. TCM has been central in treating disease for centuries in Asia, and is still widely used in modern medical practice. Herbal medicines are increasingly being used by patients in Western countries to treat various diseases including allergy and asthma. See Association BM. Complementary Medicine: new approaches to good practice. Oxford: Oxford University Press, 1993; and De Smet P A. Herbal remedies. N Engl J Med 2002; 347:2046-2056. However a role for TCM in Western medicine is uncertain because of the lack of well-controlled studies confirming their reputed effects. Laboratory and clinical investigations regarding efficacy, safety and possible mechanisms of action are required.